Malonyl-coenzyme A (malonyl-CoA) is a central metabolite in mammalian fatty acid biochemistry generated and utilized in the cytoplasm; however, little is known about noncanonical organelle-specific malonyl-CoA metabolism. Intramitochondrial malonyl-CoA is generated by a malonyl-CoA synthetase, ACSF3, which produces malonyl-CoA from malonate, an endogenous competitive inhibitor of succinate dehydrogenase. To determine the metabolic requirement for mitochondrial malonyl-CoA, ACSF3 knockout (KO) cells were generated by CRISPR/Cas-mediated genome editing. ACSF3 KO cells exhibited elevated malonate and impaired mitochondrial metabolism. Unbiased and targeted metabolomics analysis of KO and control cells in the presence or absence of exogenous malonate revealed metabolic changes dependent on either malonate or malonyl-CoA. While ACSF3 was required for the metabolism and therefore detoxification of malonate, ACSF3-derived malonyl-CoA was specifically required for lysine malonylation of mitochondrial proteins. Together, these data describe an essential role for ACSF3 in dictating the metabolic fate of mitochondrial malonate and malonyl-CoA in mammalian metabolism.
Pubmed ID: 28479296 RIS Download
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This polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Lipoic Acid
View all literature mentionsThis monoclonal targets Acaca
View all literature mentionsThis unknown targets ACSF3
View all literature mentionsThis unknown targets OXPHOS
View all literature mentionsThis monoclonal targets HSC 70 (B-6)
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis monoclonal secondary targets IgG
View all literature mentionsThis polyclonal targets succinyllysine
View all literature mentionsThis unknown targets Malonyl-Lysine [Mal-K]
View all literature mentionsThis monoclonal targets ACC
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name B6.Cg-Lepob/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Lipoic Acid
View all literature mentionsThis monoclonal targets Acaca
View all literature mentionsThis unknown targets OXPHOS
View all literature mentionsThis monoclonal targets HSC 70 (B-6)
View all literature mentionsThis unknown targets OXPHOS
View all literature mentionsThis unknown targets ACSF3
View all literature mentionsThis monoclonal targets HSC 70 (B-6)
View all literature mentionsThis monoclonal targets Acaca
View all literature mentionsThis unknown targets ACSF3
View all literature mentionsThis polyclonal targets Lipoic Acid
View all literature mentions